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Lipid nanoparticles with accessible nickel as a vaccine delivery system for single and multiple his-tagged HIV antigens

Authors Yan W, Jain A, O'Carra R, Woodward JG, Li W, Li G, Nath A, Mumper R

Published 17 July 2009 Volume 2009:1 Pages 1—11


Review by Single anonymous peer review

Peer reviewer comments 2

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Weili Yan1, Anekant Jain1, Ronan O’Carra2,  Jerold G Woodward3,  Wenxue Li4, Guanhan Li4, Avindra Nath4,  Russell J Mumper1

1Division of Molecular Pharmaceutics and the Center for Nanotechnology in Drug Delivery, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky; 3Department of Microbiology, Immunology and Molecular Genetics,  University of Kentucky, Lexington, KY, USA; 4Department of Neurology, Johns Hopkins University, Baltimore, MD, USA

Abstract: Lipid-based nanoparticles (NPs) with a small amount of surface-chelated nickel (Ni-NPs) were developed to easily formulate the human immunodeficiency virus (HIV) his-tagged Tat (his-Tat) protein, as well as to formulate and co-deliver two HIV antigens (his-p24 and his-Nef) on one particle. Female BALB/c mice were immunized by subcutaneous injection with his-Tat/Ni-NP formulation (1.5 µg his-Tat/mouse) and control formulations on day 0 and 14. The day 28 anti-Tat specific immunoglobulin G titer with his-Tat/Ni-NPs was significantly greater than that with Alum/his-Tat. Furthermore, splenocytes from his-Tat/Ni-NP-immunized mice secreted significantly higher IFN-γ than those from mice immunized with Alum/his-Tat. Although Ni-NPs did not show better adjuvant activity than Tat-coated anionic NPs made with sodium dodecyl sulfate (SDS/NPs), they were less toxic than SDS/NPs. The initial results indicated that co-immunization of mice using his-p24/his-Nef/Ni-NP induced greater antibody response compared to using Alum/his-p24/his-Nef. Co-delivery of two antigens using Ni-NPs also increased the immunogenicity of individual antigens compared to delivery of a single antigen by Ni-NPs. In conclusion, Ni-NPs are an efficient delivery system for HIV vaccines including both single antigen delivery and multiple antigen co-delivery.

Keywords: nanoparticle, nickel, HIV, antigen co-delivery, vaccine

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